OVERVIEW: What every practitioner needs to know

Are you sure your patient has congenital pneumonia? What are the typical findings for this disease?

Although rare, congenital pneumonia is an important cause of respiratory distress in the neonate. Most neonates present with signs of respiratory distress; however, this is a very non-specific symptom that can be related to multiple other illness, such as congenital heart disease, metabolic disorders or sepsis. A thorough and systematic evaluation is needed to work through this diagnostic dilemma.

The clinical signs and symptoms of congenital pneumonia may be quite subtle or overwhelming. The most common clinical symptoms are tachypnea (respiratory rate > 60) and increased work of breathing. The increased work of breathing often manifests as use of accessory respiratory muscles (i.e. nasal flaring or retractions) or grunting.

Each of these clinical symptoms is an effort to improve gas exchange by increasing minute ventilation or sustain adequate lung volumes. Indicators that the patient is failing to compensate for the impaired gas exchange include lethargy, poor feeding and apnea. Hypoxemia will eventually result in hemodynamic compromise, including acidosis, poor perfusion and hypotension.

Clinical indicators suggestive of pneumonia are confirmed based on the medical history, radiographs and physical examination findings.

Confirming a diagnosis:

Confirming a diagnosis of congenital pneumonia can be difficult because the clinical signs and symptoms and radiographic findings are often non-specific and overlap with other diseases. Diagnostic procedures to obtain tissue or respiratory cultures are of limited utility in this population. Therefore, the clinician must perform a careful assessment of available clinical and laboratory data to confirm this diagnosis.

Classic radiographic features of a congenital pneumonia include bilateral diffuse infiltrates, because most congenital pneumonias are associated with hematogenous seeding of the respiratory tract due to an underlying bacterial or viral infection. The infection and secondary inflammatory response results in edema and a generalized infiltrative process. For example, congenital syphilitic pneumonia has been described as "pneumonia alba" because the lungs are completed opacified on x-ray. Unlike pneumonia in older children, neonatal pneumonia rarely presents as a focal infiltrate but rather as bilateral homogenous opacities.

The absence of certain radiographic findings help distinguish congenital pneumonia from other diseases; however, they do not exclude the diagnosis. Air bronchograms are classically seen with hyaline membrane disease but is a non-specific finding. Radiographic findings associated with meconium or blood aspiration typically appears as patchy infiltrates which may involve one or both lungs.

Respiratory cultures obtained from intubated neonates are easy to obtain. Positive culture results can be useful in confirming a diagnosis of congenital pneumonia, particularly with congenital syphilis infection and congenital herpes infection. However, the clinician must be aware that some positive respiratory cultures only represent colonization and not true infection. We do not recommend performing routine respiratory cultures on all neonates with respiratory symptoms.

Bronchoscopy is a useful procedure to obtain respiratory cultures; however, this technology is not readily available for most clinicians and impractical in the smallest prematurely born infants. Use of bronchoscopy is typically reserved for refractory or unusual cases not responding to medical treatment.

What other disease/condition shares some of these symptoms?

A variety of physiologic and metabolic derangements create conditions in the neonate that may present as respiratory distress. Signs and symptoms of respiratory distress in the newborn is a non-specific finding that can be associated with various pulmonary and non-pulmonary disorders. Inadequate attention to detail or performing a thorough evaluation to confirm the appropriate diagnosis can result in delay of appropriate therapy and can be potentially life threatening, particularly for patients with congenital heart disease or metabolic disorders.

Outlined below is a system-based differential diagnosis of other conditions that should be considered in an infant with suspected congenital pneumonia.

Respiratory Disorders:

-Respiratory distress syndrome

-Transient tachypnea of newborn

-Meconium aspiration syndrome

-Blood or amniotic fluid aspiration

-Pleural effusion

-Primary pulmonary hypertension

Disorders of Lung Development:

-Alveolar capillary dysplasia

-Congenital diaphragmatic hernia

-Congenital lobar emphysema

-Diaphragmatic eventration

-Laryngeal stenosis

-Lung hypoplasia/agenesis

-Pulmonary sequestration

-Mutation of ABCA3 gene

-Surfactant protein B deficiency

-Tracheo-esophageal fistula

Cardiac Disorders:

-Congenital heart disease

-Pericardial effusion

-Hypertrophic cardiomyopathy

Infectious/Metabolic Disorders:

-Inborn error of metabolism

-Metabolic acidosis (primary or secondary)

-Sepsis

Neurologic Disorders:

-Brachial plexus injury

-Congenital hypotonia syndromes

What caused this disease to develop at this time?

Most causes of congenital pneumonia are infectious; therefore similar risk factors associated with early onset sepis are also associated with an increased risk of congenital pneumonia. Review of maternal history is very important to identify potential risk factors. Confirmatory laboratory tests are useful. Careful review of physical exam findings may give clues to the underlying pathogen.

Careful review of maternal history is critically important to identify maternal risk factors specific for congenital pneumonia and risk factors for certain pathogens. The maternal past medical history should be reviewed to identify a past history of previous bacterial or viral diseases that could be transmitted to the infants, including hepatitis viruses, herpes, syphilis.

Maternal risk factors associated with the perinatal period include: premature onset of labor under 37 weeks gestation, premature or prolonged rupture of membranes, maternal fever, maternal chorioamnionitis. Prenatal laboratory samples should have been collected early in gestation to screen for infection with hepaitis B, syphilis, and gonorrhea. Universal screening of all pregnant women for colonization with group B streptococcus should occur between 35-37 weeks gestation or at the time of presentation of threatened delivery. Environmental exposures may provide important clues for exposure to unusual pathogens.

Complications during the labor and delivery process can increase the risk for conditions that mimic congenital pneumonia because these infants are at risk for respiratory distress. Cesarean delivery is frequently performed for a variety of maternal conditions or concern for fetal well-being. Various physiologic processes necessary for effective clearance of fetal lung fluid are frequently impaired in neonates born at term or preterm gestation. These infants are at increased risk to develop respiratory symptoms that frequently result in admission to the neonatal intensive care unit for respiratory support.

Meconium staining of the amniotic fluid increases the potential risk for aspiration pneumonia in the neonate. Similarly, bleeding due to a placental abruption or placenta previa increases the risk for an aspiration pneumonia.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Identification of the responsible pathogen from a respiratory culture can be helpful to confirm a diagnosis of congenital pneumonia and this information can guide decision making regarding appropriate antibiotic therapy. A tracheal aspirate can readily be obtained from an intubated patient. Nasal swabs are of limited utility, but can be helpful in the patient with suspected viral pneumonia. Special stains and culture techniques may be necessary to visualize some organisms, such as the spirochete associated with congenital syphilis.

►It is important to remember that a negative respiratory culture does not exclude the diagnosis of congenital pneumonia.

The neonate with a congenital pneumonia may also have a concomitant bacteremia, therefore a blood culture should be obtained. Similarly, a complete blood count with differential can provide supportive data to substantiate suspected infection.

Most neonates with congenital pneumonia have an infiltrative process in the lung that compromises gas exchange. The clinical symptoms of tachypnea and increased respiratory effort are a physiologic attempt for the neonate to compensate for these pulmonary abnormalities. Though non-specific, pulse oximetry is a simple, accurate and reproducible method to evaluate oxygenation.

Ideally, a pre-ductal and a post-ductal oxygen saturation test should be obtained to identify any clinical evidence of pulmonary hypertension of the neonate or cardiac disease. The physiologic response to parenchymal lung disease is to increase minute ventilation by increasing respiratory rate. Most neonates can sustain this for a period of time; however, if prolonged or severe the infant may develop a respiratory acidosis. A capillary or arterial blood gas helps the clinician evaluate oxygenation and adequacy of diffusion of CO2.

Prolonged hypoxemia will ultimately result in metabolic acidosis. Similarly, blood gases can be helpful to rule out some diseases that have similar clinical presentations as congenital pneumonia, such as inborn errors of metabolism. In this scenario, lactate and ammonia levels can be helpful.

Bronchoscopy is not routinely performed in the neonate with suspected congenital pnemonia. Tissue specimens may be indicated in refractory cases not responding to medical management.

Would imaging studies be helpful? If so, which ones?

Imaging studies are an important diagnostic tool in the evaluation of a neonate with congenital pneumonia. A two view radiograph of the chest (AP and lateral view) is the most commonly used imaging study to diagnose congenital pneumonia because the study is fast, portable and of relatively low cost and low risk to the patient. Results are easily interpretable. The yield is high because most infants with a congenital pneumonia will have abnormal findings on CXR, which can include haziness in the lung fields, air bronchograms, decreased lung volumes, or a focal infiltrate.

More sophisticated imaging of the chest such as computed tomography (CT) or magnetic resonance imaging (MRI) scans are rarely necessary in the infant with congenital pneumonia; however, they can be useful in patients with atypical findings. This imaging study is fast, however, the cost is high and the yield is low. Portable neonatal scans are not readily available in many centers, therefore the infant would have to be transported.

A cardiac echocardiogram can be a very useful imaging study in the evaluation of an infant with suspected pneumonia. This imaging study should not be used on a routine basis but reserved for those infants who do not have an adequate response to the hyperoxia challenge or those with suspected pulmonary hypertension. Most centers have portable echocardiography, however, the cost is high and the yield is variable, depending on the presentation.

Confirming the diagnosis

The clinician must determine if the respiratory distress in the neonate is secondary to a respiratory disorder or a cardiac disorder. Careful review of the presentation, radiographic findings and the clinical exam should help guide a differential diagnosis. However, given the non-specific nature of the findings additional diagnostic tools are needed.

The hyperoxia challenge is a clinical tool to help differentiate cardiac disease from pulmonary disease in a neonate with respiratory symptoms and hypoxia. Figure 1 outlines the decision making algorithm.

Figure 1.

Hypoxia challenge

If you are able to confirm that the patient has congenital pneumonia, what treatment should be initiated?

Various types of respiratory support are available and selection is based on the clinical findings for each specific patient. In a patient with hypoxemia but adequate ventilation, supplemental oxygen via nasal cannula may be sufficient. However, infants with more severe blood gas abnormalities may require CPAP, mechanical ventilation or high frequency ventilation. Extracorporeal membrane oxygenation (ECMO) is available for the most extreme cases unresponsive to medical management. Additional respiratory support may be necessary to maintain adequate lung volumes and overcome diffusion abnormalities.

Antibiotic therapy should be started as soon as possible: Empiric antibiotic therapy for suspected congenital pneumonia should be initiated as soon as possible until culture results are available or other potential causes of the respiratory distress are identified. The vast majority of cases of congenital pneumonia are caused by bacterial pathogens associated with early onset sepsis. Careful review of the maternal history is necessary to identify potential sources of infection. Rarely, viral infections are associated with congenital pneumonia. Appropriate antiviral therapy, if available, should be initiated in these cases.

Infants with congenital pneumonia often have evidence of multi-system organ dysfunction. Hemodynamic instability is common in the critically ill neonate; therefore, appropriate adjustments are necessary for fluid and electrolyte management. Ionotropes should be used as clinically indicated. Metabolic acidosis is not uncommon and treatment should focus on treating the underlying cause resulting in acidosis.

Congenital pneumonia is typically a short term disease that occurs during the first week of life; however, some infants require long term management. In severe cases in which infants require prolonged respiratory support, some develop secondary lung injury resulting in longer term respiratory symptoms. For example, infants with syphilitic pneumonia (pneumonia alba) are more likely to develop lung fibrosis. The oxidant stress associated with prolonged exposure of the neonatal lung to high concentrations of oxygen and barotrauma can also occur. Many of these severely affected infants will require supplemental oxygen at discharge or have the need for prolonged ventilator support.

Tracheostomy is necessary for those who require long term ventilation.

Treatment options include appropriate choice of antibiotic and support for any evidence of associated organ dysfunction. The choice of antibiotic is based on the suspected underlying pathogen. Recommended duration of therapy is 7-10 days. Sensitivity profiles from culture results can be helpful in selecting antibiotic choice. There are limited options for treatment of suspected viral pneumonia.

What are the adverse effects associated with each treatment option?

Most therapies for treatment of congenital pneumonia are supportive and of short duration. The risk for adverse short term effect can be minimized by appropriate attention to detail and monitoring. Similarly, long term adverse effects are unusual because therapy is typically supportive in nature and of short duration.

Supplemental oxygen:

Frequently required in the treatment of patients with congenital pneumonia. Prolonged exposure to high concentrations of inspired oxygen can result in secondary oxidant injury to the lung. This inflammatory cascade contributes to the risk of chronic lung disease in severely affected neonate. This risk is minimized by tenacious monitoring of oxygen saturations to avoid hyperoxia and monitoring of blood gases to quantify adequacy of oxygen delivery.

Mechanical ventilation:

Extremely effective in improving gas exchange in neonates with pneumonia; however, the associated barotrauma can cause secondary injury to the lung. Judicious use of pressure is important to minimize barotrauma to the lungs. The appropriate mode of ventilation should be selected to optimize gas exchange while minimizing injury to the lung.

Antibiotic therapy:

A critical component of effective treatment of congenital pneumonia. The risk/benefit analysis strongly favors the use of antimicrobial therapy in any patient with suspected pneumonia. Allergic reactions in the neonate are exceedingly rare. Prolonged use of broad spectrum antibiotic therapy has been associated with colonization by resistant microorganisms and fungal infection. These complications are rarely seen associated with a defined 7-10 day course of therapy.

Affected infants may have evidence of multi-system organ dysfunction and are typically kept NPO during the acute stage of respiratory distress. Fluid and electrolyte management should based on adequacy of renal function and overall hemodynamic status. Frequent monitoring of electrolytes in recommended.

Careful monitoring of the patient's blood pressure and perfusion are important indicators of hemodynamic compromise. Some agents used to support cardiac functioning may cause tachycardia.

What are the possible outcomes of congenital pneumonia?

What will you tell the family about prognosis?

-Majority of infants survive

-Mortality estimated between 5-10% (higher risk for preterm infants)

-Majority do not require oxygen after the acute disease has resolved

-Majority will not have ongoing respiratory illnesses

-A small percentage of infants fail to respond to maximal medical therapy and respiratory support. These children should be evaluated as potential candidates for extracorporeal membrane oxygenation (ECMO), which may require transfer to another center which provides a higher level of care.

What will you tell the family about risks/benefits of the available treatment options?

The potential benefits of treatment with oxygen, respiratory support and antibiotics strongly outweigh potential risk of medical therapy.

The risks associated with ECMO are specifically related to that therapy and are not affected by initiation of treatment for pneumonia. The risks associated with ECMO must be balanced against the severity of lung disease and respiratory failure.

What causes this disease and how frequent is it?

Epidemiology

The incidence of congenital pneumonia is variable with reported estimates ranging from 5-50/1000 live births annually. The incidence varies between term and preterm infants, with prematurely born infants being at higher risk for infection. These estimates likely represent an ascertainment bias because the signs of symptoms of congenital pneumonia overlap with many of neonatal conditions and many cases are likely unreported.

It is often difficult for the clinican to distinguish congenital pneumonia from other comorbid neonatal conditions. By definition, this disease is present at birth, therefore cases are typically diagnosed among infants who become symptomatic within the first 24-48 hours after birth. There is not a seasonal variation.

Mode of transmission

The mode of transmission is similar to other early onset infections. The infection most likely occurs either transplacentally, as an ascending infection or by aspiration of infected amniotic fluid. Predisposing exposures include GBS colonization, untreated or inadequately treated maternal syphilis, maternal herpes simplex virus infection, maternal cytomegalovirus (CMV) infection or maternal exposure to cats infected with toxoplasmosis.

How do these pathogens/genes/exposures cause the disease?

Maternal infection or colonization serves as the primary route of infection that results in congenital pneumonia. The interface between the maternal and fetal circulation creates a unique environment that will allow infection in the fetus from the mother by transplacental infection, ascending infection or aspiration of infected amniotic fluid.

Maternal colonization with a variety of pathogens serves as one of the most important risk factors for neonatal infection, including congenital pneumonia. The organism ascends from the vaginal canal into the amniotic fluid. Transplacental infection occurs when the agent enters the fetal circulation and proceeds to infect multiple organs, including the lungs.

Interestingly, most infants with congenital pneumonia have negative blood cultures. The fetus swallows amniotic fluid throughout gestation, therefore they can aspirate infected amniotic fluid and develop pneumonia. Additionally, aspiration during the peripartum period is not uncommon.

What complications might you expect from the disease or treatment of the disease?

The majority of neonates with congenital pneumonia have no long term complications; however, a small percentage develop chronic lung disease and require respiratory support after the acute infection has resolved. Infants with congenital syphilitic pneumonia are at higher risk for chronic lung disease because this infection causes focal obliterative fibrosis and scarring of the lungs. Many neonates with a history of severe respiratory disease during the neonatal period will have problems with reactive airway disease, particularly within the first 12 months after birth.

Are additional laboratory studies available; even some that are not widely available?

C-reactive protein - not diagnostic but could be used to monitor inflammatory response.

How can congenital pneumonia be prevented?

Strategies to prevent congenital pneumonia focus on appropriate management of maternal conditions and exposures that result in an increased risk of infection in the neonate.

Prevention of early onset GBS disease will decrease the incidence of congenital GBS associated pneumonia. Compliance with published guidelines from the Centers for Disease Control and Prevention (CDC) and American College of Obstetrics and Gynecology (ACOG) are necessary for the appropriate identification of the colonized mother and subsequent peripartum antibiotic prophylaxis prior to delivery.

Vaccine trials are ongoing to prevent GBS disease. Mothers who have had a previous child infected with invasive GBS disease should be appropriately counseled about the importance of sharing this information with her medical providers in all subsequent pregnancies because their infant should be screened, treated and observed for at least 48 hours after delivery.

Premature onset of labor and/or prolonged rupture of membranes have both been associated with an increased risk of perinatal infection. Appropriate obsterical management for these mothers, including timely administration of antibiotic therapy, is an important prevention strategy.

Avoiding missed opportunities to obtain prenatal labs to screen for potential maternal infection is yet another important prevention strategy. A systems based approach to ensure that appropriate documentation is available at the time of presentation for delivery is important for all pregnant women, particularly those with risk factors for infection.

What is the evidence?

(Despite substantial progress in prevention of perinatal group B streptococcal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States. In 1996, CDC, in collaboration with relevant professional societies, published guidelines for the prevention of perinatal group B streptococcal disease [CDC. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45{No. RR-7}]; those guidelines were updated and republished in 2002 [CDC. Prevention of perinatal group B streptococcal disease: revised guidelines from CDC. MMWR 2002;51{No. RR-11}].In June 2009, a meeting of clinical and public health representatives was held to reevaluate prevention strategies on the basis of data collected after the issuance of the 2002 guidelines. This report presents CDC's updated guidelines, which have been endorsed by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the American College of Nurse-Midwives, the American Academy of Family Physicians, and the American Society for Microbiology. The recommendations were made on the basis of available evidence when such evidence was sufficient and on expert opinion when available evidence was insufficient.The key changes in the 2010 guidelines include the following: * expanded recommendations on laboratory methods for the identification of GBS, * clarification of the colony-count threshold required for reporting GBS detected in the urine of pregnant women, * updated algorithms for GBS screening and intrapartum chemoprophylaxis for women with preterm labor or preterm premature rupture of membranes, * a change in the recommended dose of penicillin-G for chemoprophylaxis, * updated prophylaxis regimens for women with penicillin allergy, and * a revised algorithm for management of newborns with respect to risk for early-onset GBS disease.Universal screening at 35-37 weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns. Although early-onset GBS disease has become relatively uncommon in recent years, the rates of maternal GBS colonization [and therefore the risk for early-onset GBS disease in the absence of intrapartum antibiotic prophylaxis] remain unchanged since the 1970s.Continued efforts are needed to sustain and improve on the progress achieved in the prevention of GBS disease. There also is a need to monitor for potential adverse consequences of intrapartum antibiotic prophylaxis [e.g., emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens]. In the absence of a licensed GBS vaccine, universal screening and intrapartum antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease prevention.)

(Most newborns are born vigorous and do not require neonatal resuscitation. However, about 10% of newborns require some type of resuscitative assistance at birth. Although the vast majority will require just assisted lung aeration, about 1% requires major interventions such as intubation, chest compressions, or medications.Recently, new evidence has prompted modifications in the international cardiopulmonary resuscitation [CPR] guidelines for both neonatal, pediatric and adult patients. Perinatal and neonatal health care providers must be aware of these changes in order to provide the most appropriate and evidence-based emergency interventions for newborns in the delivery room.The aim of this article is to provide an overview of the main recommended changes in neonatal resuscitation at birth, according to the publication of the international Liaison Committee on Resuscitation [ILCOR] in the CoSTR document [based on evidence of sciences] and the new 2010 guidelines released by the European Resuscitation Council [ERC], the American Heart Association [AHA], and the American Academy of Pediatrics [AAP].)

Ongoing controversies regarding etiology, diagnosis, treatment

Some organisms have been identified from the lungs of neonates, however, the clinical significance associated with the presence of these pathogens remains somewhat unclear. Additional research is needed, particularly in vulnerable low birth populations.

Ureaplasma urealyticum has been isolated from the amniotic fluid of pregnant women and from the tracheal aspirate of neonates. The presence of this organism does not universally correlate with clinical evidence of disease therefore its significance is unclear. There are very limited data in term populations and data in preterm infants have been variable. This infection can be associated with a severe inflammatory response in the lung or no clinical disease at all.

There are case reports of neonatal infection with the novel H1N1 virus. Published data are extremely limited in both term and preterm populations. There are rare case reports of infected neonates with clinical symptoms. There appears to be an increased risk to the fetus of newborn of a mother who becomes infected with this virus during the peripartum period. Routine immunization of pregnant women is recommended by the CDC.